Periodic Reporting for period 1 - RHYTHM (Engineered Heart Tissue (EHT) Devices based on Ion Conductive Guanosine-Quadruplex (GQ) Hydrogels: A Route to Advance In Vitro 3D Cardiac Tissue Models)
Okres sprawozdawczy: 2023-09-01 do 2025-08-31
Globally, myocardial infarction is the primary cause of death among cardiac patients, needing the urgent development of new approaches in the fields of tissue engineering and regenerative medicine. From a tissue engineering perspective, novel cardiac 3D culture models of high physiological relevance are key to accelerate our understanding of human heart diseases and our ability to rapidly screen potential new drugs, thereby leading to new personalized treatments. Although in vitro preclinical models for cardiovascular disease have been reported, they still do not entirely recapitulate the important features of the native cardiac tissue. In the last decade, one of such platforms called human Engineered Heart Tissues (EHT) have emerged as affordable in vitro models for cardiac research. In EHTs, cardiac cells are embedded in a soft hydrogel material, then introduced in a microfluidic platform for cell culture under controlled conditions to prompt the formation of cardiac tissue, which in turn can be used as a model to study cardiovascular diseases and to test new treatments. Despite the progress achieved, traditional hydrogels used in EHT are inherently non-conductive and thus non-ideal as scaffolds, which limits the physiological relevance and applicability of these models.
The RHYTHM project was designed to address this challenge by developing bioinspired conductive hydrogels that replicate the physiological microenvironment that native cells find in cardiac tissue. These new hydrogels serve as soft, biocompatible scaffolds capable of conducting electrical signals, an essential feature for maintaining synchronized heart contractions in these artificial tissues. The main scientific objective of this project was to develop a biomaterial-based platform for applications in cardiovascular disease modelling. We aimed to develop a bioinspired injectable hydrogel scaffold with conductive properties to provide a more favorable microenvironment for cardiac tissue formation. Our approach was to synthesize self-assembled ion-conductive guanosine-quadruplex (GQ) hydrogels, which were then tested in the fabrication of advanced EHT platforms.
By integrating biomaterials science, microfabrication technologies, and cell biology, RHYTHM sought to establish a foundation for next-generation in vitro cardiac tissue models that bridge the gap between traditional cell culture systems and in vivo models. As such, this project contributes to the EU’s Horizon Europe goals of advancing health research, reducing the need for animal testing, and accelerating the development of safe and effective therapies for heart disease.
The RHYTHM project was designed to address this challenge by developing bioinspired conductive hydrogels that replicate the physiological microenvironment that native cells find in cardiac tissue. These new hydrogels serve as soft, biocompatible scaffolds capable of conducting electrical signals, an essential feature for maintaining synchronized heart contractions in these artificial tissues. The main scientific objective of this project was to develop a biomaterial-based platform for applications in cardiovascular disease modelling. We aimed to develop a bioinspired injectable hydrogel scaffold with conductive properties to provide a more favorable microenvironment for cardiac tissue formation. Our approach was to synthesize self-assembled ion-conductive guanosine-quadruplex (GQ) hydrogels, which were then tested in the fabrication of advanced EHT platforms.
By integrating biomaterials science, microfabrication technologies, and cell biology, RHYTHM sought to establish a foundation for next-generation in vitro cardiac tissue models that bridge the gap between traditional cell culture systems and in vivo models. As such, this project contributes to the EU’s Horizon Europe goals of advancing health research, reducing the need for animal testing, and accelerating the development of safe and effective therapies for heart disease.
Throughout the project RHYTHM, we focused on designing and optimizing conductive GQ supramolecular hydrogels suitable for cell culture and for integration into EHT platforms. The main goal of this project was to develop physiologically relevant biomaterials that can be used to induce the formation of mature cardiac tissue. The research involved specific objectives such as i) synthesis of ion-conductive GQ hydrogels and ii) investigation of their relevant properties such as physical chemical stability, mechanical strength, morphology, ionic conductivity, and cytocompatibility; thus iii) ensuring that they could support the growth and synchronized beating of cardiac cells within EHT platforms. The project then established one step further towards in vitro cardiac models by culturing human cardiac cells within the innovative ion-conductive GQ hydrogels.
RHYTHM served as a framework to accomplish training objectives that went beyond achieving the project research goals. This included specific technical training, such as enhancing the researcher’s knowledge of biomaterials engineering through the synthesis of GQ hydrogels, broadening the applied methods to characterize their physical chemical, mechanical, ion-conductive, and biological properties, and the capability to apply them to advance in vitro modeling. Additionally, the researcher was able to improve her career prospects through scientific communication, dissemination, and new collaborations in the framework of this project. In this way, RHYTHM contributes not only to European scientific excellence but also to social awareness of sustainable biomaterials and biomedical innovation. The project outcomes were shared through several international and national conference presentations, collaborative meetings, outreach events as well as several manuscripts for scientific publications (in progress), altogether making its findings accessible to other researchers, policy makers, and the general public.
RHYTHM served as a framework to accomplish training objectives that went beyond achieving the project research goals. This included specific technical training, such as enhancing the researcher’s knowledge of biomaterials engineering through the synthesis of GQ hydrogels, broadening the applied methods to characterize their physical chemical, mechanical, ion-conductive, and biological properties, and the capability to apply them to advance in vitro modeling. Additionally, the researcher was able to improve her career prospects through scientific communication, dissemination, and new collaborations in the framework of this project. In this way, RHYTHM contributes not only to European scientific excellence but also to social awareness of sustainable biomaterials and biomedical innovation. The project outcomes were shared through several international and national conference presentations, collaborative meetings, outreach events as well as several manuscripts for scientific publications (in progress), altogether making its findings accessible to other researchers, policy makers, and the general public.
Results Beyond the State of the Art
RHYTHM advanced the field of cardiac tissue models by creating ionically conductive, bioinspired GQ hydrogels that combine mechanical integrity with precise tunability of ion-conductivity and cytocompatibility properties. Throughout this project, we gained a fundamental scientific understanding of these synthetic GQ hydrogels with intrinsic ion-conductive capabilities as an attractive alternative to replace traditional (non-conductive) matrices (e.g. fibrin or Matrigel) for cardiac cell embedding in fabrication of EHT models. This represents a major step beyond existing in vitro cardiac models, which currently rely on non-conductive scaffolds that fail to reproduce the physiological conditions of the native human heart.
In addition to scientific advances, the project generated new interdisciplinary knowledge connecting biomaterials design, 3D cell culture studies and microfluidics-based bioengineering technologies. These insights open new avenues for the creation of smart scaffolds for tissue regeneration, further extending RHYTHM’s impact beyond the laboratory.
RHYTHM advanced the field of cardiac tissue models by creating ionically conductive, bioinspired GQ hydrogels that combine mechanical integrity with precise tunability of ion-conductivity and cytocompatibility properties. Throughout this project, we gained a fundamental scientific understanding of these synthetic GQ hydrogels with intrinsic ion-conductive capabilities as an attractive alternative to replace traditional (non-conductive) matrices (e.g. fibrin or Matrigel) for cardiac cell embedding in fabrication of EHT models. This represents a major step beyond existing in vitro cardiac models, which currently rely on non-conductive scaffolds that fail to reproduce the physiological conditions of the native human heart.
In addition to scientific advances, the project generated new interdisciplinary knowledge connecting biomaterials design, 3D cell culture studies and microfluidics-based bioengineering technologies. These insights open new avenues for the creation of smart scaffolds for tissue regeneration, further extending RHYTHM’s impact beyond the laboratory.